- New formulation of old aspirin for better delivery
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For better use of cyclooxygenase dependent anti-inflammatory properties and mitochondrial activities of aspirin, new hydrophobic analogues of aspirin were developed and successfully encapsulated in polymeric nanoparticles (NPs). In vivo anti-inflammatory effects of these NPs using a mouse model demonstrated unique properties of an optimized aspirin analogue to inhibit production of pro-inflammatory and enrichment of anti-inflammatory cytokines.
- Kalathil, Akil A.,Kumar, Anil,Banik, Bhabatosh,Ruiter, Timothy A.,Pathak, Rakesh K.,Dhar, Shanta
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- Heterogeneous Rupturing Dendrimers
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Utilizing macromolecular scaffolds as templates for the production of small molecules that are distinctively different from the original monomer feedstock has many potential applications. Herein, as a proof-of-concept, a family of dendrimers displaying internally queued disulfide bridges were synthesized and exploited as flawless macromolecular templates that selectively rupture into a set of monomeric mercaptans. Disassembly was accomplished in a reducing environment, using DTT as an external stimulus, and the thiol constituents were successfully isolated. Their composition was dictated by three dendritic regions, i.e., (i) the symmetrical trithiol of the core (C3), (ii) the interior-asymmetric trithiols (CD2), and (iii) the periphery-asymmetric monothiols (DB2), in which B functionality is of an orthogonal nature. Taking into account the steady state between disulfides and thiols in all living cells, the collapse of the dendrimers to a multitude of smaller thiols was intracellularly assessed as a means to disrupt the balance of reactive oxygen species (ROS) often elevated in cancer cells. Indeed, the fragmentation induced a significant increase of ROS in human lung carcinoma A549 cells. These findings can potentially alter the perception of dendrimers being limited to carriers to being prodrugs for intracellular delivery of ROS with the potential to fight cancer.
- Andrén, Oliver C. J.,Fernandes, Aristi P.,Malkoch, Michael
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- Oriented nanoporous lamellar organosilicates templated from topologically unsymmetrical dendritic-linear block copolymers
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Dendrimers between the sheets: Environmentally responsive dendritic-linear block copolymers, based on poly(ethylene oxide) and a dendron derived from 2,2′-bis(hydroxymethyl)propionic acid (see structure), were used to organize organosilicate vitrificates into nanostructured lamellar morphologies. Upon thermolysis of the template, a perforated porous lamellar structure (4 nm) between organosilicate sheets (6-9 nm) was obtained. (Chemical Equation Presented).
- Magbitang, Teddie,Lee, Victor Y.,Cha, Jennifer N.,Wang, Hsiao-Lin,Chung, W. Richard,Miller, Robert D.,Dubois, Geraud,Volksen, Willi,Kim, Ho-Cheol,Hedrick, James L.
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- Self-assembled micelles of well-defined pentaerythritol-centered amphiphilic A4B8 star-block copolymers based on PCL and PEG for hydrophobic drug delivery
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Biodegradable star-shaped poly(ε-caprolactone) (PCL) with four arms were synthesized by ring-opening polymerization (ROP) from a symmetric pentaerythritol core via the ''core-first'' strategy. Subsequently, two samples of the amphiphilic A4B8 star-block copolymers with symmetrical topologies [4s(PCL-b-2sPEG)] were synthesized by a macromolecular coupling reaction between carboxyl-terminated poly(ethylene glycol) (PEG) and 4-arm star-shaped PCL macromers with eight -OH end groups. The latter was prepared by attaching 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid (HHMPA) to 4sPCL using a simple two-step reaction sequence. The in vitro cytotoxicity test indicated no apparent cytotoxicity. The amphiphilic star-block copolymers are capable of self-assembling into spherical micelles in water at room temperature, and they possess low critical micelle concentrations (CMCs) of 2~8 mg/L in aqueous solution which was determined by fluorescence spectroscopy using pyrene as a probe. Transmission electron microscopy (TEM) measurement demonstrated that the micelles exhibit a spherical shape with a size range of 30~50 nm in diameter. In addition, the hydrophobic and anticancer drug, quercetin, is loaded effectively in the polymeric micelles, suggesting that these new materials are appropriate candidates as hydrophobic drug nanocarriers.
- Nabid, Mohammad Reza,Tabatabaei Rezaei, Seyed Jamal,Sedghi, Roya,Niknejad, Hassan,Entezami, Ali Akbar,Oskooie, Hossein Abdi,Heravi, Majid M.
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- Synthesis, Micellization, and Surface Activity of Novel Linear-Dendritic Carboxylate Surfactants
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Two generations of novel linear-dendritic carboxylate surfactants C18-G1-(COONa)2 and C18-G2-(COONa)4 have been synthesized by the divergent method and their structures are characterized by 1H Nuclear Magnetic Resonance and Infrared analysis. The electrical conductivity measurement is used to measure the Krafft temperatures of C18-G1-(COONa)2 and C18-G2-(COONa)4, which are much smaller than those of the corresponding conventional surfactant sodium stearate. The markedly enhanced solubility of two linear-dendritic surfactants is ascribed to the high hydrophilicity of surfactant headgroups induced by the carboxylate and ester groups. The critical micelle concentration (CMC) values obtained from both the electrical conductivity and surface tension measurements indicate that the micellizations of linear-dendritic surfactants become favorable with the increase in the number of the surfactant headgroup. However, the surface activity parameters including the surface tension at the CMC, maximum surface excess, and minimum surface area reveal that C18-G1-(COONa)2 exhibits greater efficiency in absorbing at the air/water interface compared to C18-G2-(COONa)4, owing to their different steric repulsions of the surfactant headgroups. In addition, C18-G1-(COONa)2 and C18-G2-(COONa)4 have higher emulsifying ability than the conventional surfactants sodium stearate and sodium octadecyl sulfate.
- Lou, Yuning,Dong, Yajuan,Wang, Xiaoyong,Gong, Feirong,Zhao, Min,Rong, Zongming
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- Evaluation of thermal and oxidative stability of three generations of phenolic based novel dendritic fuel and lubricant additives
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Antioxidants, particularly those designed for use in hydrocarbon media, suffer from a variety of limitations including high volatility and poor solubility. Using 2,2-bis(hydroxymethyl)propionic acid as the branching unit, a series of novel dendrons featuring 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic ester chain ends have been synthesised to provide improved solubility of such hindered phenolic antioxidants. The thermal stability, assessed by thermogravimetric analysis, revealed that all the functionalised dendrons have enhanced thermal stability when compared to commercial antioxidants (BHT, Irganox L135 and Irganox L57). Antioxidant ability was evaluated using pressurised differential scanning calorimetry and when blended with a lubricant base oil, at 0.5% w/w, an increase in antioxidant performance was observed when compared to the commercial antioxidants.
- Higgins, Clare L.,Filip, Sorin V.,Afsar, Ashfaq,Hayes, Wayne
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- Catalytically active hybrid polyurethane with tetraaniline pendant groups: Synthesis, properties and self assembly
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For the first time we report a novel hybrid polyurethane synthesized from tetraaniline-diol (TAni-(OH)2) and hexamethylene diisocyanate (HMDI) with pendant tetraaniline units on the back bone. The striking property of this unprecedented polyurethane is its electrochemical sensing of ascorbic acid and self assembly into core-shell type microstructures (microcapsules) in presence of aqueous acetic acid/n-octane interface. These microcapsules exhibited a wide range of pH responses in their absorption spectrum. The synthesized polyurethane containing pendant tetraaniline units showed good surface conductivity to the tune of 3.4 × 10-4 S/cm. The electrochemical investigation showed two single electron oxidations and two single electron reductions reversibly. We also investigated electrochemical sensing details of carbon paste electrode (CPE) fabricated with conducting polyurethane (TANI-PU) as ascorbic acid sensor (vitamin C, AA) in 0.2 M and pH 7 phosphate buffer solution. The fabricated electrode is useful in sensing as low as 1 mM of ascorbic acid. Self-assembly property was probed by optical and TEM studies which established the core-shell structure of the assembled species. The self assembled microcapsules exhibited pH dependent doping and dedoping processes as established by UV-Vis study.
- Arukula, Ravi,Rao, Chepuri R.K.,Narayan, Ramanuj,Sreedhar
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- Iodine-Containing Mass-Defect-Tuned Dendrimers for Use as Internal Mass Spectrometry Calibrants
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Calibrants based on synthetic dendrimers have been recently proposed as a versatile alternative to peptides and proteins for both MALDI and ESI mass spectrometry calibration. Because of their modular synthetic platform, dendrimer calibrants are particular
- Giesen, Joseph A.,Diament, Benjamin J.,Grayson, Scott M.
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- Molecular brushes with extreme grafted side chain densities
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A series of densely grafted poly(n-butyl acrylate) (PBA) molecular brushes with four different grafting densities were synthesized by the "grafting-from" approach using atom transfer radical polymerization (ATRP). A novel monomer, isopropylidene-2,2-Bis(methoxy)propionic hydroxyethylmethacrylate (IMPHMA), was synthesized and copolymerized with methyl methacrylate (MMA) under different monomer feed ratios to yield a series of linear poly(methyl methacrylate-stat-IMAPA), [PMMA-s-(PIMPHMA)]. The resulting copolymers were deprotected and transformed to macroinitiators, [PMMA-s-(PHEMA-IMPHMA-Br)]. n-Butyl acrylate (BA) was grafted from these macroinitiators to yield a series of molecular brushes, [PMMA-s-{(PIMPHMA)-g- PBA}], with various side chain lengths. Molecular brushes were characterized by gel permeation chromatography (GPC) and 1H NMR. PBA side chains were cleaved by acid hydrolysis, and the resulting linear PBA polymers were characterized by GPC to study initiation efficiency during the synthesis of molecular brushes. The initiation efficiency increased with polymerization time and decreased with macroinitiators that had more initiation sites. Atomic force microscopy (AFM) measurements demonstrated the characteristic molecular structure by resolving individual brush molecules.
- Bak, Jae Min,Jha, Gourishanker,Ahn, Eungjin,Jung, Seo-Hyun,Jeong, Han Mo,Kim, Byeong-Su,Lee, Hyung-Il
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- Development of l-Amino-Acid-Based Hydroxyl Functionalized Biodegradable Amphiphilic Polyesters and Their Drug Delivery Capabilities to Cancer Cells
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Hydroxyl-functionalized amphiphilic polyesters based on l-amino acid bioresources were designed and developed, and their nanoassemblies were explored as intracellular enzyme-biodegradable scaffolds for delivering anticancer drugs and fluorophores to cancer cells. To accomplish this task, acetal-masked multifunctional dicarboxylic ester monomer from l-aspartic acid was tailor-made, and it was subjected to solvent-free melt transesterification polycondensation with commercial diols to produce acetal-functionalized polyesters. Acid-catalyzed postpolymerization deprotection of these acetal-polyesters produced amphiphilic hydroxyl-functionalized polyesters. The amphiphilic polyesters were self-assembled in aqueous medium to produce nanoparticles of size 200 nm. Wide ranges of both water-soluble and water-insoluble anticancer drugs such as doxorubicin (DOX), camptothecin (CPT), and curcumin (CUR) and fluorophores such as Nile red (NR), Rose Bengal (RB), and Congo red (CR) were encapsulated in hydroxyl polyesters nanoparticles. In vitro drug release studies revealed that the aliphatic polyester backbone underwent lysosomal enzymatic-biodegradation to release the loaded cargoes at the intracellular compartments. Lysotracker-assisted live-cell confocal microscopy studies further confirmed the colocalization of the polymer nanoscaffolds in the lysosomes and supported their enzymatic-biodegradation for drug delivery. In vitro cytotoxicity studies showed that the nascent polymers were not toxic, whereas their anticancer drug-loaded nanoparticles exhibited excellent cell killing in cervical cancer (HeLa) cell lines. The drug-loaded (CPT, CUR, and DOX) and the fluorophore-loaded (NR, RB, and CR) polymer nanoparticles were highly luminescent; thus, the encapsulated polymer nanoparticles enabled the multiple color-tunable bioimaging in cancer cells in the entire visible region from blue to deep red. Time-dependent live-cell confocal microscopy studies established that the cellular uptake of drugs and fluorophores was 5 to 10-fold higher while they were delivered from the hydroxyl polyester platform. The hydroxyl polyester nanocarrier design strategy opens up new opportunities in drug delivery to cancer cells from a biodegradable polymer platform based on l-amino acids.
- Saxena, Sonashree,Jayakannan, Manickam
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- "Click" synthesis of intrinsically hydrophilic dendrons and dendrimers containing metal binding moieties at each branching unit
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A new family of water-soluble triazole dendrimers composed of tri(ethylene glycol) (TrEG) and bis(methylol)propionic acid (bis-MPA) was created through Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) between specifically designed complementary building blocks. Dendrimers up to generation three were synthesized by CuAAC to a trifunctional core with yields ranging from 72% for generation one, through 67% for generation two, and 64% for third generation dendrimer. The two triazole rings at each bis-MPA branching site could serve as efficient chelating pockets for some VIIIA group elements. As proof-of-principle, the [PdCl2(PhCN)2] coordination chemistry of these hydrophilic dendritic ligands was studied by 1H NMR, dynamic light scattering, transmission electron microscopy, and DFT calculations. The results showed that the complexation is completed within 5 min. The novel hydrophilic dendritic Pd complexes were able to catalyze Suzuki-Miyaura coupling reactions in water within 3 h at 100 °C, at 60 °C, and even at 50 °C with practically quantitative conversion.
- Wang, Lili,Kiemle, David J.,Boyle, Connor J.,Connors, Eoghan L.,Gitsov, Ivan
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- Synthesis of a novel macroinimer based on thiophene and poly(ε-caprolactone) and its use in electrochromic device application
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Synthesis of a novel macroinimer comprising poly(ε-caprolactone) (PCL) and thiophene (Th) and its use in electrochromic device (ECD) application have been reported. First, a novel Th monomer (5) with miktofuntional initiator groups (primary hydroxyl and tertiary bromide at the third position of the thiophene ring) was synthesized in a four-step reaction sequence. Density functional theory-predicted bond lengths, angles, and vibrations of 5 were in good agreement with available experimental vibrational spectra. Subsequently, ring-opening polymerization of ε-caprolactone (ε-CL) was carried out in bulk using 5 as the initiator and tin(II) 2-ethylhexanoate (Sn(Oct) 2) as the catalyst at 115 °C, which led to α-thiophene end-capped PCL macroinimer (PCL-Th). Furthermore, PCL-Th macroinimer was used in electrochemical copolymerization with pyrrole (Py) and Th. PCL-Th/PTh copolymer film synthesized on indium tin oxide-coated glass slide showed electrochromic behavior. Optical analyses of the PCL-Th/PTh copolymer film indicated that the copolymer film was suitable to be used as an anodically coloring material for ECD applications.
- Kucuk, Asuman Celik,Yilmaz, Faruk,Can, Hatice,Durmaz, Hakan,Kosemen, Arif,Muftuoglu, Ali Ekrem
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- Formation kinetics and scaling of "defect-free" hyperbranched polystyrene chains with uniform subchains prepared from seesaw-type macromonomers
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Using a facile approach, we successfully made large "defect-free" hyperbranched polystyrene (PSt) chains with uniform subchains between two branching points from the interchain "clicking" of a seesaw-type linear macromonomer [azide~~~alkyne~~~azide] prepared by ATRP with a following conversion of two bromine-ends into two azide-ends, where ~~~ denotes a PSt chain (1.65-31.0 kg/mol). The "click" reaction kinetics monitored by a combination of size exclusion chromatography (SEC) and laser light scattering (LLS) reveals that the degree of self-polycondensation (DP) is related to the reaction time (t) as ln(DP+ 1)/2 = ([A]0kAB,0)/β arctan(βt), where [A]0 and kAB,0 are the initial alkyne concentration and the initial reaction rate between the azide and alkyne groups, respectively; β is a constant and its reciprocal (1/β) represents the time at which k AB = kAB,0/2. The results reveal that 1/β is scaled to the macromonomer's molar concentration ([C]) and molar mass (M) as 1/β ~ [C]-0.35M0.55, indicating that 1/β is governed by the interchain distance and diffusion, respectively. Each hyperbranched sample can be further fractionated into a set of narrowly distributed "defect-free" hyperbranched chains with different molar masses by precipitation. The LLS results show, for the first time, that the root-mean-square radius of gyration (〈Rg〉) and hydrodynamic radius (〈Rh〉) of "defect-free" hyperbranched polystyrenes in toluene at 25 °C are scaled to the weight-average molar mass (Mw) as 〈Rg〉 = 5.53 × 10 -2Mw0.464 and 〈Rh〉 = 2.95 × 10-2Mw0.489, respectively, where the exponents are smaller than the predicted 1/2.
- Li, Lianwei,He, Chen,He, Weidong,Wu, Chi
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- Highly effective ion-pair receptors based on 2,2-bis(aminomethyl)-propionic acid
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Compounds 2 and 3 were designed and prepared as heteroditopic ion-pair receptors. The design features a 2,2-bis(aminomethyl)propionic acid core to connect and pre-organize binding groups. The cation binding is provided by a sodium selective N-acyl aza-18-crown-6 subunit whereas for anion complexation, two urea groups (receptor 2) or two squaramide groups (receptor 3) were introduced. Beyond acting as anion binding sites, the urea and squaramide groups were used to support sodium cation complexation through metal carbonyl oxygen lone pair interactions. The receptors were found to bind sodium salts of chloride, bromide and nitrate much more strongly than the corresponding ions accompanied by counterions that do not coordinate to the receptor. For example, chloride binding to receptor 2 enhances the strength of sodium complexation by up to 23 times. Conversely, sodium binding enhances chloride recognition by a factor of three. Receptor 3 containing squaramide units, binds sodium chloride and bromide with a similar albeit lower cooperativity. Moreover, unprecedentedly tight binding of these salts was achieved, with association constants as high as log Ka = 6.52 M-1 for NaCl salt complexation.
- Za?ubiniak, Dominika,Zakrzewski, Maciej,Pi?tek, Piotr
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- Accelerated Chemoselective Reactions to Sequence-Controlled Heterolayered Dendrimers
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Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.
- García-Gallego, Sandra,Andrén, Oliver C. J.,Malkoch, Michael
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- Construction of Janus dendrimers through a self-assembly approach involving chiral discrimination at a focal point
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A strategy to build Janus dendrimersviathe chirality-directed self-assembly of heteroleptic Zn(ii) BOX complexes is reported. The method allows quantitative synthesis of Janus dendrimersin situwithout the need for purifications. Each dendritic domain of t
- Zhou, John,Cole, Ashley M.,Menuey, Elizabeth M.,Kilway, Kathleen V.,Moteki, Shin A.
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supporting information
p. 6404 - 6407
(2021/07/02)
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- One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA
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Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.
- Zhang, Dapeng,Atochina-Vasserman, Elena N.,Maurya, Devendra S.,Huang, Ning,Xiao, Qi,Ona, Nathan,Liu, Matthew,Shahnawaz, Hamna,Ni, Houping,Kim, Kyunghee,Billingsley, Margaret M.,Pochan, Darrin J.,Mitchell, Michael J.,Weissman, Drew,Percec, Virgil
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supporting information
p. 12315 - 12327
(2021/08/20)
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- TWO-WAY MAGNETIC RESONANCE TUNING NANOPROBE ENHANCED SUBTRACTION IMAGING
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The present invention provides a nanocarrier having an interior and an exterior, the nanocarrier comprising: a plurality of amphiphilic compounds that self-assemble to form the nanocarrier; and a first magnetic resonance imaging (MRI) contrast agent and a
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Paragraph 0039; 0145
(2021/06/26)
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- Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms
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Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weig
- Garciá-Gallego, Sandra,Stenstr?m, Patrik,Mesa-Antunez, Pablo,Zhang, Yuning,Malkoch, Michael
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p. 4273 - 4279
(2020/11/09)
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- Strictly sparse surface modification and its application for endowing nanoparticles with an exact "valency"
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Sparsely modified surfaces can be used as a general platform for precisely modifying small nanoparticles. However, strictly, rather than statistically, sparse surface modification remains a big challenge. Herein, we report a new and general method for str
- Yang, Ruiqi,Dou, Jinkang,Jiang, Li,Chen, Daoyong
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supporting information
p. 15553 - 15556
(2020/12/30)
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- NRTI THERAPIES
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Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.
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Page/Page column 36
(2020/07/14)
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- Side chain type liquid crystal epoxy monomer, preparation method thereof and side chain type liquid crystal epoxy resin
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The invention provides a side chain type liquid crystal epoxy monomer, a preparation method thereof and a side chain type liquid crystal epoxy resin, and belongs to the technical field of epoxy resinmaterials. The molecular structure of the side chain typ
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Paragraph 0052; 0090-0091
(2020/06/17)
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- Orthophthalic dihydroxyl macromolecular carrier and application thereof in construction of drug complex nano delivery system
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The invention belongs to the field of medicine and relates to an orthophthalic dihydroxyl macromolecular carrier reversibly bindable to a drug, a drug-macromolecular complex formed by the orthophthalic dihydroxyl macromolecular carrier and a drug, and a nano delivery system constructed with the drug-macromolecular complex. The orthophthalic dihydroxyl macromolecular carrier prepared herein can reversibly bind with the drug to form the drug-macromolecular complex and a nano particle delivery system, has the evident advantage of high drug-carrying capacity, and helps implement reduction of drugtoxicity, improvement of drug stability, improvement of in-vivo targeting property of the drug and enhancement of drug efficacy; experimental results show that the drug-macromolecular complex and itsnano particle delivery system feature pH responsive drug release, drug toxicity can be evidently reduced, drug stability can be improved, passive targeting action is given to play in vivo, or active targeting action is given to play after target molecular are further modified, and efficacy of the drug is markedly improved. The orthophthalic dihydroxyl macromolecular carrier and the system herein have a good clinical application prospect.
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Paragraph 0028; 0030; 0031
(2019/03/26)
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- Cationic poly(ester amide) dendrimers: Alluring materials for biomedical applications
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Novel cationic poly(ester amide) dendrimers have been synthesized by copper(i) azide-alkyne cycloaddition (CuAAC) of a tripropargylamine core and azide-terminated dendrons, in turn prepared by iterative amide coupling of the new monomer 2,2′-bis(glycyloxymethyl)propionic acid (bis-GMPA). The alternation of ester and amide groups provided a dendritic scaffold that was totally biocompatible and degradable in aqueous media at physiological and acidic pH. The tripodal dendrimers naturally formed rounded aggregates with a drug that exhibited low water solubility, camptothecin, thus improving its cell viability and anti-Hepatitis C virus (anti-HCV) activity. The presence of numerous peripheral cationic groups enabled these dendrimers to form dendriplexes with both pDNA and siRNA and they showed effective in vitro siRNA transfection in tumoral and non-tumoral cell lines.
- Lancelot, Alexandre,González-Pastor, Rebeca,Clavería-Gimeno, Rafael,Romero, Pilar,Abian, Olga,Martín-Duque, Pilar,Serrano, José L.,Sierra, Teresa
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supporting information
p. 3956 - 3968
(2018/06/21)
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- Method for preparing temsirolimus
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The invention discloses a method for preparing temsirolimus. The method comprises the following steps: (1) preparing 2,2,5-trimethyl-5-carboxy-1,3-dioxane; (2) cooling the 2,2,5-trimethyl-5-carboxy-1,3-dioxane and dichloromethane to 0-5 DEG C under the protection of nitrogen, performing stirring for dissolving, adding DIPEA and 2,4,6-trichlorobenzoyl chloride, and carrying out a reaction to obtainan acid anhydride product; (3) adding the acid anhydride product to dichloromethane containing rapamycin and 4-(N,N-dimethylamino)pyridine, and carrying out a reaction; and (4) mixing a product obtained in step (3) with tetrahydrofuran containing p-toluenesulfonic acid, dropwise adding ethylene glycol at 0-5 DEG C, adding water after the reaction is finished, performing extraction by using ethylacetate, and washing and drying the extracted product to prepare the temsirolimus. The method has the advantages of simple preparation process, high yield, high purity and low cost, and is suitable for industrialized production.
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Paragraph 0028; 0029; 0052; 0054-0055
(2018/04/03)
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- Biocompatable monomer biliary tract computer tomography contrast agent comprising iodine and manufacturing method thereof
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The present invention relates to a contrast agent for biocompatible monomer biliary tract computer tomography containing iodine, and a manufacturing method thereof. According to the present invention, a biocompatible biliary tract CT contrast agent is pro
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Paragraph 0066; 0067-0072
(2019/03/07)
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- NOVEL DERIVATIVES OF CURCUMINOIDS AND USE THEREOF AS AN ANTICANCER AGENT
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A series of novel bis(hydroxymethyl) alkanoate derivatives of curcuminoids were designed, and synthesized, which show anticancer activity, and in particular to breast cancer, colon cancer, and prostate cancer.
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Paragraph 40
(2018/02/03)
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- Design and synthesis of dendrimers with facile surface group functionalization, and an evaluation of their bactericidal efficacy
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We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click") reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1-3 with 8-32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH3+ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers.
- Ladd, Elizabeth,Sheikhi, Amir,Li, Na,Van De Ven, Theo G.M.,Kakkar, Ashok
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- MODIFICATION OF DRUGS FOR INCORPORATION INTO NANOPARTICLES
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Aspirin is chemically modified to generate a prodrug that releases aspirin in cellular milieu. The prodrug has a lipophilic tail that may enhance uptake efficiency in nanoparticles. Nanoparticles including the prodrugs may be effective for treating inflammatory disorders, including neurodegenerative disorders.
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Paragraph 0135; 0136; 0137
(2017/08/01)
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- PHOTOACID COMPOUND, PHOTOACID GENERATOR AND PREPARATION METHOD THEREOF, AND RESIST COMPOSITION COMPRISING PHOTOACID GENERATOR
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The invention is related to a photoacid generator and a resist agent composition including the photoacid generator, which adjusts acid diffusion from an exposed area to an unexposed area in a forming process of a resist film, so as to decrease line edge r
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Paragraph 0061
(2016/10/08)
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- DENDRITIC COMPOUNDS, PHOTORESIST COMPOSITIONS AND METHODS OF MAKING ELECTRONIC DEVICES
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Dendritic compounds are provided. The dendritic compounds include an anionic dendron that has a focal point having an anionic group and a linking group, and a photoreactive cation. The dendritic compounds find particular use as photoacid generators. Also
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Paragraph 0058
(2016/11/28)
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- Synthesis process for temsirolimus
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The invention discloses a synthesis process for temsirolimus. The synthesis process comprises the following steps: step 1, preparing 2,2,5-trimethyl-5-carboxyl-1, 3-dioxane; step 2, preparing anhydride; step 3, carrying out esterification reaction; step 4, carrying out hydrolysis reaction and finally obtaining the target product, temsirolimus. According to the synthesis process disclosed by the invention, in the reaction of the step 2, DIPEA (diisopropanolamine) is selected as alkali and methylene chloride is selected as a solvent so that anhydride reaction liquid can be directly used in the reaction in the step 3, and technological operation is reduced; the selectivity of the direct esterification reaction is achieved by lowering the temperature and controlling the usage amount of DMAP (dimethylaminopyridine) and the usage amount of anhydride, and the by-products of 31-esterification are reduced; the esterification selectivity is improved greatly, and the reaction route is simplified; and by selecting an ethylene glycol, para-toluenesulfonic acid and tetrahydrofuran deprotection system, the reaction time is reduced greatly, and the yield is improved.
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Paragraph 009; 0010
(2016/12/26)
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- Acrylic monomer, polymer and a resist composition comprising the polymer
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The present invention relates to an acryl monomer of the following chemical formula 1, which is useful as a monomer for forming an anticorrosive additive, a polymer for anticorrosive additive including a repeating unit derived from the same and a resist composition including the same. The polymer includes a repeating unit derived from the acryl monomer of the following chemical formula 1. In performing a micromachining process by immersion lithography, the hydrophobicity of a surface of a resist film in an exposure process may be elevated, thereby inhibiting the resist film being digested by water. The resist film is changed into hydrophilic in a developing process after exposure, so that a surface of the resist film has a lower static contact angle, thereby a fine resist pattern having excellent photosensitivity and resolution can be formed. Chemical formula 1 (the definition of each substituent in the formula is as described in the description).
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Paragraph 0268-0270
(2017/01/09)
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- Self-assembling amphiphilic Janus dendrimers: Mesomorphic properties and aggregation in water
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The self-assembly behaviour both in bulk and in water of amphiphilic dendrimeric derivatives based on bis-MPA is the central theme of this article. The designed molecules possess two parts with different polarity; this feature is the key factor that forces their self-assembly in water into supramolecular architectures, due to hydrophobic interactions between the lipophilic fractions of the molecules, and the appearance of mesomorphic order in bulk in response to a variation of temperature (thermotropic liquid crystals). The effects provoked by the hydrophilic/lipophilic balance of the molecule were studied varying the generation of the corresponding dendrons and combining them via CuAAC click chemistry in order to obtain symmetrical and unsymmetrical final Janus dendrimers. The ability of the aggregates formed in water to encapsulate hydrophobic drugs has also been explored.
- Fedeli, Elisabetta,Lancelot, Alexandre,Serrano, José Luis,Calvo, Pilar,Sierra, Teresa
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supporting information
p. 1960 - 1967
(2015/03/18)
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- Dendron-Mediated Engineering of Interparticle Separation and Self-Assembly in Dendronized Gold Nanoparticles Superlattices
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Self-assembly of nanoparticles into designed structures with controlled interparticle separations is of crucial importance for the engineering of new materials with tunable functions and for the subsequent bottom-up fabrication of functional devices. In t
- Jishkariani, Davit,Diroll, Benjamin T.,Cargnello, Matteo,Klein, Dahlia R.,Hough, Lawrence A.,Murray, Christopher B.,Donnio, Bertrand
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supporting information
p. 10728 - 10734
(2015/09/28)
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- High loaded dendrimers with free peripheral groups
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We report the synthesis of dendrons and dendrimers with branching units composed of two parts: a residue with biological activity and a branching molecule. This approach allows better exploitation of the dendritic architecture, giving to the scaffolding s
- Valencia-Gallegos, Jesús A.,álvarez, Mario M.,Martínez-Merino, Víctor J.
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supporting information
p. 6803 - 6806
(2018/03/26)
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- Synthesis of poly(ester-amide) dendrimers based on 2,2-Bis(hydroxymethyl) propanoic acid and glycine
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Water-soluble, biodegradable, and biocompatible poly(ester-amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB2 adduct of 2,2-bis(hydroxymethyl) propanoic acid (bis-MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester-amide) dendrimers as well as commercially available bis-MPA dendrimers, poly(ester-amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water-solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation.
- Pahovnik, David,?usak, Anja,Reven, Sebastjan,?agar, Ema
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p. 3292 - 3301
(2016/02/18)
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- Degradation kinetics of model hyperbranched chains with uniform subchains and controlled locations of cleavable disulfide linkages
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We developed a strategy to make model hyperbranched structure with uniform subchains and controlled locations of cleavable linkages. First, a novel seesaw-type tetrafunctional initiator with one alkyne, one disulfide linkage, and two bromine groups (≡-S-S-(Br)2) was prepared. Using such an initiator, an AB2-type macromonomer (azide~~alkyne~ ~azide) with one disulfide linkage at its center was prepared via successive atom transfer radical polymerization (ATRP) and azidation substitution reaction, where ~~ represents polystyrene chains. Further interchain "clicking" coupling between the azide and alkyne groups on the macromonomers led to model hyperbranched polystyrenes with uniform subchains and controllablly located cleavable disulfide linkages. The 1H nuclear magnetic resonance spectra, Fourier transform infrared spectroscopy, and size exclusion chromatography with a multiangle laser light scattering detector confirmed the designed degradable hyperbranched structure. Armed with this novel sample, we studied its dithiothreitol (DTT)-induced degradation in various organic solvents by a combination of static and dynamic LLS. We found that the cleavage of disulfide bonds contains a fast and a slow process. The fast one reflects the degradation of disulfide bonds on the chain periphery; while the slow one involves those inside. Both the fast and slow degradation reaction rate constants (Kfast and Kslow) are a linear function of the initial DTT concentration ([DTT]0), but the relative contribution of the two processes is mainly governed by the hyperbranched chain structure, nearly independent of [DTT]0.
- Li, Lianwei,Wang, Xu,Yang, Jinxian,Ye, Xiaodong,Wu, Chi
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p. 650 - 658
(2014/02/14)
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- HIGH MOLECULAR WEIGHT ZWITTERION-CONTAINING POLYMERS
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The present invention provides multi-armed high MW polymers containing hydrophilic groups and one or more functional agents, and methods of preparing such polymers.
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Paragraph 0297; 0298
(2014/02/16)
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- HETEROCYCLIC INHIBITORS OF GLUTAMINASE
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The invention relates to the heterocyclic compounds of Formula (I) as defined further herein, and pharmaceutical preparations thereof. The invention further relates to methods of treating cancer, immunological or neurological diseases using the heterocyclic compounds of the invention.
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Page/Page column 64; 65
(2013/06/06)
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- PROCESS FOR THE PREPARATION OF RAPAMYCIN DERIVATIVES
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The invention relates to processes for the preparation of compound of CCI-779 having the Formula (I), which is useful as an antineoplastic agent. The invention further relates to certain novel intermediates useful in the preparation of compound of CCI-779 and processes for their preparation. The invention also relates to pharmaceutical compositions that include the compound of CCI-779, prepared according to the processes disclosed herein.
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Page/Page column 12
(2012/08/27)
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- PROCESS FOR THE PREPARATION OF RAPAMYCIN DERIVATIVES
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The invention relates to processes for the preparation of compound of CCI-779 having the Formula (I), which is useful as an antineoplastic agent. The invention further relates to certain novel intermediates useful in the preparation of compound of CCI-779 and processes for their preparation. The invention also relates to pharmaceutical compositions that include the compound of CCI-779, prepared according to the processes disclosed herein.
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Page/Page column 22
(2011/05/11)
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- Thermosensitive dendrimer formulation for drug delivery at physiologically relevant temperatures
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A simple and versatile dendrimer based platform to deliver therapeutic agents at temperatures within the physiological range, is reported. Lipoic acid conjugated at the periphery of the thermosensitive dendrimer formulations undergoes slow and sustained release at 37-42 °C, and rescues the cells from oxidative stress and a pro-inflammatory endotoxic agent. The Royal Society of Chemistry 2011.
- Castonguay, Annie,Wilson, Eleanor,Al-Hajaj, Noura,Petitjean, Laurene,Paoletti, Julie,Maysinger, Dusica,Kakkar, Ashok
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supporting information; experimental part
p. 12146 - 12148
(2011/12/15)
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- NOVEL PYRROLINONE DERIVATIVE AND MEDICINAL COMPOSITION CONTAINING SAME
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The present invention provides a novel P2X3 and/or P2X2/3 receptor antago nist. A compound represented by the formula (I): wherein Z1 is optionally protected hydroxy, etc.; Z2 is -C(=O)-, etc.; Z
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Page/Page column 217
(2011/07/06)
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- Degradable self-assembling dendrons for gene delivery: Experimental and theoretical insights into the barriers to cellular uptake
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This paper uses a combined experimental and theoretical approach to gain unique insight into gene delivery. We report the synthesis and investigation of a new family of second-generation dendrons with four triamine surface ligands capable of binding to DN
- Barnard, Anna,Posocco, Paola,Pricl, Sabrina,Calderon, Marcelo,Haag, Rainer,Hwang, Mark E.,Shum, Victor W. T.,Pack, Daniel W.,Smith, David K.
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supporting information; scheme or table
p. 20288 - 20300
(2012/02/05)
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- Self-assembling ligands for multivalent nanoscale heparin binding
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Supramolecular string of pearls: Polycationic ligands are designed to self-assemble into spherical pseudo-dendrimers that are capable of binding polyanionic heparin with affinities and binding modes similar to covalent nanostructures such as dendrimers an
- Rodrigo, Ana C.,Barnard, Anna,Cooper, James,Smith, David K.
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scheme or table
p. 4675 - 4679
(2011/06/27)
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- BENZENE SULFONAMIDE THIAZOLE AND OXAZOLE COMPOUNDS
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The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 132
(2011/06/16)
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- Process for preparation of temsirolimus
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The present invention provides two synthetic routes for the preparation of Temsirolimus (compound 1b and analog of Temsirolimus 1a). The first route includes the synthesis of CCI-779 by directly reacting rapamycin (4b) or Prolyl-rapamycin (4a) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base, followed by deprotection to give CCI-779 or Proline CCI-779. The second route includes a process involving a reaction of rapamycin-OH-31-sily ether (4d) or Prolyl-rapamycin-OH-31-sily ether (4c) with substituent-2,2-bis(methoxy) propionic acid anhydride(11) in the presence of an organic base and followed by subsequent hydrolysis step to obtain the desired CCI-779 or Proline CCI-779. Compound 11, as described in this invention, is stable at room temperature, cost effective and ease of processing.
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Page/Page column 12
(2010/10/19)
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- Effect of crosslinker multiplicity on the gel point in ATRP
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The experimental gelation was studied in atom transfer radical polymerization (ATRP) of methyl acrylate (MA) with various branching reagents that structurally differ by the number of vinyl groups (multiplicity). MA was copolymerized with branching reagent
- Van Camp, Wim,Gao, Haifeng,Prez, Filip E.Du.,Matyjaszewski, Krzysztof
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experimental part
p. 2016 - 2023
(2011/02/28)
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- Combined CuI-catalysed alkyne-azide cycloaddition and furan-maleimide Diels-Alder "click" chemistry approach to thermoresponsive dendrimers
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A divergent dendrimer construction methodology that employs Cu I-catalysed alkyne-azide cycloaddition (CuAAC) and furan-maleimide Diels-Alder (DA) "click" chemistry in a layer-by-layer fashion, is described. This synergisitic approach yields dendrimers that undergo thermal disassembly via a retro-DA reaction. The Royal Society of Chemistry 2010.
- Vieyres, Arnaud,Lam, Tina,Gillet, Renaud,Franc, Gregory,Castonguay, Annie,Kakkar, Ashok
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scheme or table
p. 1875 - 1877
(2010/06/16)
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